Abstract
Previous reports demonstrated the effectiveness of silibinin hemisuccinate as a potential intraocular pressure-lowering agent. The exact mechanism by which silibinin exerted this effect has not yet been documented, but might suggested to interfere with aqueous humor formation. The present study was designed to evaluate the comparative efficacy of silibinin as IOP lowering agent to that of betaxolol in normotensive rabbits, and the interaction of silibinin with betaxolol as a way for investigating the possible mechanism of action of silibinin in this respect. The effects of instillation of 0.75% silibinin solution and 0.5% betaxolol eye drops in the eyes of normotensive rabbits were evaluated using indentation tonometry. The results showed that 0.75% solution of silibinin was more potent than betaxolol (0.5%) in lowering IOP in normotensive rabbits. Furthermore, the effect of pre- and post-instillation of silibinin-betaxolol combination showed a characteristic antagonistic feature. In conclusion, silibinin appears to be more potent than betaxolol in lowering IOP in normotensive rabbits; the pre- and post-instillation of silibinin provide experimental evidence for the possible antagonistic effect of betaxolol with the IOP-lowering effect of silibinin.
 Key words: silibinin, betaxolol, cAMP, PDE-inhibitors
Highlights
Glaucoma is no longer defined as elevated intraocular pressure (IOP) but rather a condition comprises characteristic optic nerve head and visual filed abnormalities [1], lowering IOP is still the major strategy in slowing down glaucomatous damage to the inner structures of the eye and visual filed [2]
Since agonists to all βadrenergic receptors (β1, β2, and β3) stimulate adenylcyclase via interaction with Gs-protein to increase cAMP production, betaxolol was thought to lower IOP by reducing the intracellular concentrations of cAMP [16]. It has long been unclear whether the putative reduction in cAMP itself causes the reduction in IOP, an observation reported by Liu et al (1981) who demonstrated that Dtimolol, another β-blocker might be as effective as L-timolol in decreasing aqueous flow [17], despite stereospecificity of the βadrenergic receptors for the L-isomers [18]
A conflicting result have recently been reported by McLaughlin et al (2001) who demonstrated that application of cAMP did not reverse timolol’s effects; and that timolol and levobunolol produced cAMP-independent inhibition of the regulatory volume increase (RVI) in ciliary cells and increased intracellular Ca2+ and pH; they suggested that inhibition of Cl-/HCO3- exchange mediates timolol’s inhibition of aqueous humor formation as an alternative mechanism for the reduction of aqueous inflow and IOP [7]
Summary
Glaucoma is no longer defined as elevated intraocular pressure (IOP) but rather a condition comprises characteristic optic nerve head and visual filed abnormalities [1], lowering IOP is still the major strategy in slowing down glaucomatous damage to the inner structures of the eye and visual filed [2]. The ciliary epithelium has α2- and 2-adrenergic receptors. Topical instillation of epinephrine decreases the rate of AH formation, an effect thought to be mediated by. -receptor induced increase in cAMP in the ciliary epithelium [5]. The participation of cAMP in this effect has been supported by finding that activators of adenylcyclase (cholera toxin and forskolin) decrease AH formation and IOP in experimental animals and human [6]. Targeting of this Cltransport system is thought to be the newer proposed mechanism for the lowering of IOP by the oldest antiglaucomatus drug, Timolol[7]
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Schedule a callMore From: Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)
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